The Combination Chemotherapy of SIRIOX as First- or Second-Line Chemotherapy for Pancreatic Cancer

Pancreatic cancer (mainly pancreatic ductal adenocarcinoma, PDAC) is a disease with extremely poor prognosis, and is often fatal. Surgical resection is the only potentially curative technique for management of PDAC, but only approximately 15% to 20% of patients are candidates for pancreatectomy at the time of diagnosis Gemcitabine (Gem) is widely used as a standard chemotherapeutic agent for advanced pancreatic cancer. FOLFIRINOX (fluoropyrimidine/leucovorin plus irinotecan and oxaliplatin), compared with Gem, has been proved to significantly improve the objective response rate (31.6% VS. 9.4%, P \< 0.001) and prolong the median survival time (11.1 months VS. 6.8 months, P \< 0.001) for patients with metastatic pancreatic ductal adenocarcinoma(PDAC), who had a performance status of ECOG 0-1 score. However, it is undeniable that the adverse effects of FOLFIRINOX are severe. For example, the incidence of 3/4 grade neutrophil decrease in patients receiving FOLFIRINOX is significantly higher than those with Gem (45.7% VS. 21%, P \< 0.001). Thus, it is difficult for many patients to receive standard FOLFIRINOX and benefit from the protocol. Therefore, the investigators aim to explore an improvement program of FOLFIRINOX, hoping to better benefit patients. S-1 is a new oral fluoropyrimidine derivative in which tegafur is combined with two 5-chloro-2, 4-dihydroxypyridine modulators and oteracil potassium, a potentiator of 5-fluorouracil's (5-FU's) antitumor activity that also decreases gastrointestinal toxicity. Combination chemotherapy with Gem and S-1 is reportedly well tolerated and benefits patients with advanced PDAC. Based on the results of the GEST study, S-1 is found to be non-inferior to Gem in patients' survival. Therefore, in this study, the investigators replaced 5-FU and leucovorin in the FOLFIRINOX regimen with oral S-1, forming a SIRIOX regimen to treat patients with advanced pancreatic cancer, as first- or second-line chemotherapy.